Systems and methods for delivering drugs

ABSTRACT

A patch pump device generally includes at least one fluid source, a fluid communicator, and an electrochemical actuator. The fluid communicator is in fluid communication with the fluid source. The electrochemical actuator is operative to cause fluid to be delivered from the fluid source into the fluid communicator.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application Ser.No. 60/952,217, filed Jul. 26, 2007. This application also claims thebenefit of U.S. Provisional Application Ser. No. 60/989,605, filed Nov.21, 2007. Both of these applications are incorporated herein byreference.

BACKGROUND OF THE INVENTION

This invention is generally in the field of medical devices, and moreparticularly in the field of drug delivery devices.

Drug delivery involved delivering a drug or other therapeutic compoundinto the body. Typically, the drug is delivered via a technology that iscarefully selected based on a number of factors. These factors includebut are not limited to the characteristics of the drug, such as drugdose, pharmacokinetics, complexity, cost, and absorption, thecharacteristics of the desired drug delivery profile (such as uniform,non-uniform, or patient-controlled), the characteristics of theadministration mode (such as the ease, cost, complexity, andeffectiveness of the administration mode for the patient, physician,nurse, or other caregiver), or other factors or combinations of thesefactors.

Conventional drug delivery technologies present various challenges. Oraladministration of a dosage form is a relatively simply delivery mode,but some drugs may not achieve the desired bioavailability and/or maycause undesirable side effects if administered orally. Further, thedelay from time of administration to time of efficacy associated withoral delivery may be undesirable depending on the therapeutic need.While parental administration by injection may avoid some of theproblems associated with oral administration, such as providingrelatively quick delivery of the drug to the desired location,conventional injections may be inconvenient, difficult toself-administer, and painful or unpleasant for the patient. Furthermore,injection may not be suitable for achieving certain delivery/releaseprofiles, particularly over a sustained period of time.

Passive transdermal technology, such as a conventional transdermalpatch, may be relatively convenient for the user and may permitrelatively uniform drug release over time. However, some drugs, such ashighly charged or polar drugs, peptides, proteins and other largemolecule active agents, may not penetrate the stratum corneum foreffective delivery. Furthermore, a relatively long start-up may berequired before the drug takes effect. Therefore, the drug release maybe relatively continuous, which may be undesirable in some cases. Also,a substantial portion of the drug payload may be undeliverable and mayremain in the patch once the patch is removed.

Active transdermal systems, including iontophoresis, sonophoresis, andporation technology, may be expensive and may yield unpredictableresults. Only some drug formulations, such as aqueous stable compounds,are suited for active transdermal delivery. Further, modulating orcontrolling the delivery of drugs using such systems may not be possiblewithout using complex systems.

Infusion pump systems may be large and may require tubing between thepump and the infusion set, impacting quality of life. Further, infusionpumps may be expensive and may not be disposable. From the above, itwould be desirable to provide new and improved drug delivery systems andmethods that overcome some or all of these and other drawbacks.

SUMMARY OF THE INVENTION

A patch pump device generally includes at least one fluid source, afluid communicator, and at least one electrochemical actuator. The fluidcommunicator is in fluid communication with the fluid source. Theelectrochemical actuator is operative to cause fluid to be deliveredfrom the fluid source into the fluid communicator.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic block diagram illustrating an embodiment of afluid delivery system.

FIG. 2 is a schematic view of an embodiment of an electrochemicalactuator, wherein FIG. 2( a) illustrates the electrochemical actuator ina charged state and FIG. 2( b) illustrates the electrochemical actuatoras it discharges.

FIG. 3 is a schematic view of another embodiment of an electrochemicalactuator, wherein FIG. 3( a) illustrates the electrochemical actuator ina charged state and FIG. 3( b) illustrates the electrochemical actuatoras it discharges.

FIG. 4 is a side cross-sectional view of an embodiment of a pump device,wherein FIG. 4( a) illustrates the pump device in an unassembledposition; FIG. 4( b) illustrates the pump device in an assembledposition; and FIG. 4( c) illustrates the pump device pumping fluidtherefrom.

FIG. 5 illustrates another embodiment of a pump device, wherein FIG. 5(a) is a top plan view of the pump device in an unassembled position;FIG. 5( b) is a side cross-sectional view of the pump device in theunassembled position; FIG. 5( c) is a top plan view of the pump devicein an assembled position; and FIG. 5( d) is a side cross-sectional viewof the pump device in the assembled position.

FIG. 6 is a side cross-sectional view of another embodiment of a pumpdevice, wherein FIG. 6( a) illustrates a needle insertion mechanismbeing attached to a base portion of the pump device; FIG. 6( b)illustrates the needle insertion mechanism inserting a needle andcannula through the base portion of the pump device; FIG. 6( c)illustrates the pump device in an unassembled position; and FIG. 6( d)illustrates the pump device in an assembled position.

FIG. 7 is a side cross-sectional view of another embodiment of a pumpdevice, wherein FIG. 7( a) illustrates the pump device in an unassembledposition and FIG. 7( b) illustrates the pump device in an assembledposition.

FIG. 8 is a side cross-sectional view of another embodiment of a pumpdevice, wherein FIG. 8( a) illustrates the pump device in an unassembledposition and FIG. 8( b) illustrates the pump device in an assembledposition.

FIG. 9 is a schematic illustrating an embodiment of an electricalcircuit that may be used in an embodiment of a pump device.

FIG. 10 is a graph illustrating one exemplary, non-limiting embodimentof a displacement curve, indicating the displacement behavior as afunction of time for an electrochemical actuator positioned in theelectrical circuit of FIG. 9.

FIG. 11 is a graph illustrating one exemplary, non-limiting embodimentof a fluid flow curve, indicating the fluid flow behavior as a functionof time for a fluid source associated with the electrical circuit ofFIG. 9.

FIG. 12 is a schematic illustrating an embodiment of an electricalcircuit that includes electrical contacts.

FIG. 13 is a schematic illustrating an embodiment of an electricalcircuit that includes a variable resistor.

FIG. 14 is a schematic illustrating an embodiment of an electricalcircuit that includes a switch.

FIG. 15 is a graph illustrating a displacement curve, indicating thedisplacement behavior as a function of time for a fluid sourceassociated with the electrical circuit of FIG. 14.

FIG. 16 is a schematic view of an embodiment of a device that includesan embodiment of a control system.

FIG. 17 is a side cross-sectional view of an embodiment of a pump devicethat includes multiple fluid sources operated by differentelectrochemical actuators.

FIG. 18 is a side cross-sectional view of an embodiment of a pump devicethat includes multiple fluid sources operated by the sameelectrochemical actuator.

DETAILED DESCRIPTION OF THE INVENTION

Described below are embodiments of systems and methods of delivering afluid, which may include a drug, into a patient in need thereof. Thepatient may be a human or other mammal for example. In embodiments, thesystems and methods may embody a pump device suited for subcutaneous orintravenous delivery of a fluid, which may or may not include one ormore drugs. The pump device may employ an electrochemical actuator,which may have characteristics of both a battery and a pump.Specifically, the electrochemical actuator may include anelectrochemical cell that produces a pumping force as the celldischarges. Thus, the pump device may have relatively fewer parts than aconventional drug pump, such that the pump device is relatively morecompact, disposable, and reliable than conventional drug pumps. Theseattributes of the pump device may permit reducing the cost and thediscomfort associated with infusion drug therapy. Further, such a pumpdevice may have a control means, such as a controller and/or othercircuitry, operative to regulate drug or fluid flow from the pumpdevice. Such control means may permit implementing one or more releaseprofiles using the pump device, including release profiles that requireuniform flow, non-uniform flow, continuous flow, discontinuous flow,programmed flow, scheduled flow, user-initiated flow, or feedbackresponsive flow, among others. Thus, the pump device may effectivelydeliver a wider variety of drug therapies than other pump devices.

FIG. 1 is a schematic block diagram illustrating an embodiment of afluid delivery system 100. The fluid delivery system 100 generallyincludes an electrochemical actuator 102 associated with a fluid source104 and a fluid communicator 106. The fluid source 104 may contain afluid to be delivered into a target 108 via the fluid communicator 106.The electrochemical actuator 102 may actuate or otherwise create apumping force to deliver the fluid from the fluid source 104 into thefluid communicator 106. Specifically, the electrochemical actuator 102may be any device that experiences a change in volume or position inresponse to an electrochemical reaction that occurs therein. Forexample, the electrochemical actuator 102 may include a chargedelectrochemical cell, and at least a portion of the electrochemical cellmay actuate as the electrochemical cell discharges. Thus, theelectrochemical actuator 102 may be considered a self-powered actuatoror a combination battery and actuator.

In use, the fluid communicator 106 may be associated with the target108, and the electrochemical actuator 102 may be operated. Specifically,the electrochemical actuator 102 may discharge and actuate. Theresulting mechanical work may act on the fluid source 104 or may betransferred through intervening mechanics to the fluid source 104,causing the fluid to be delivered through the fluid communicator 106into the target 108.

In embodiments, the fluid delivery system 100 may be a system fordelivering a drug into a human body. In such embodiments, the fluidsource 104 may be a reservoir, pouch, or bladder, or other known fluidsource containing a drug in fluid form, and the target 108 may be ahuman in need of a drug therapy or prophylaxis. The fluid communicator106 may be a needle, catheter, cannula, infusion set, or other knowndelivery device that is inserted into or otherwise associated with thehuman body for drug delivery. When the electrochemical reaction isoccurring in the electrochemical actuator 102, the electrochemicalactuator 102 may cause the drug to be communicated from the fluid source104 into the human body. Such drug delivery may be subcutaneous,intravenous, intraarterial, intramuscular, intracardiac, intraosseous,intradermal, intrathecal, intraperitoneal, intraumoral, epidural, and/orperi-neural depending on, for example, the location of the fluidcommunicator 106 and/or the entry location of the drug.

In embodiments, the fluid delivery system 100 may be used to deliver adrug formulation which comprises a drug, meaning a therapeutic orprophylactic agent including an active pharmaceutical ingredient. Inother embodiments, the fluid delivery system 100 may deliver a fluidthat does not contain a drug. For instance, the fluid may be a salinesolution or a diagnostic agent, such as a contrast agent.

The drug may be in a pure form or formulated in a solution, asuspension, or an emulsion, among others, using one or morepharmaceutically acceptable excipients known in the art. For example, apharmaceutically acceptable vehicle for the drug may be provided, whichmay be essentially any aqueous or non-aqueous vehicle known in the art.Examples of aqueous vehicles include physiological saline solutions,solutions of sugars such as dextrose or mannitol, and pharmaceuticallyacceptable buffered solutions, and examples of non-aqueous vehiclesinclude fixed vegetable oils, glycerin, polyethylene glycols, alcohols,and ethyl oleate. The vehicle may further include antibacterialpreservatives, antioxidants, tonicity agents, buffers, stabilizers, orother components.

Representative examples of drugs that may be delivered with embodimentsof the present invention include, but are not limited to, opioidnarcotics such as fentanyl, remifentanyl, sufentanil, morphine,hydromorphone, oxycodiene and salts thereof; NonSteroidalAntiInflamatories (NSAIDs) such as diclofenac, naproxen, ibuprofin, andcelecoxib; local anesthetics such as lidocane, tetracaine, andbupivicaine; dopamine antagonists such as apomorphine, rotigotine, andropinerole; drugs used for the treatment and/or prevention of allergiessuch as antihistamines, antileukortienes, anticholinergies, andimmunotherapeutic agents; antipastics such as tizanidine and baclofin;vitamins such as nitacin; Selegiline; and rasagiline. Essentially anypeptide, protein, bioligic, or oligonucleotide, among others, that isnormally delivered by subcutaneous, intramuscular, or intravenousinjection or other parental routes, may be delivered using embodimentsof the devices described herein. In embodiments, the device may be usedto administer a drug combination of two or more different drugs using asingle or multiple delivery port and being able to deliver the agents ata fixed ratio or by means enabling the delivery of each agent to beindependently modulated. For example, two or more drugs can beadministered simultaneously or serially, or a combination (e.g.overlapping) thereof.

Although the fluid delivery system 100 and other systems and methodsdescribed herein are generally described as communicating drugs into ahuman body, such systems and methods may be employed to deliver anyfluid of any suitable biocompatibility or viscosity into any object,living or inanimate. For example, the systems and methods may beemployed to deliver other biocompatible fluids into living beings,including human beings and other animals. Further the systems andmethods may deliver drugs or other fluids into living beings other thanhuman beings, such as animals and plant life. Also, the systems andmethods may deliver any fluids into any target, living or inanimate. Thesystems and methods described herein are generally systems and methodsof delivering fluids using an electrochemical actuator, including aself-powered actuator and/or combined battery and actuator.

Embodiments of such electrochemical actuators are generally described inU.S. patent application Ser. No. 11/150,477 entitled “ElectrochemicalMethods, Devices, and Structures” by Chiang et al., U.S. patentapplication Ser. No. 11/881,830 entitled “Electrochemical Actuator” byChiang et al., each of which is herein incorporated by reference. Suchelectrochemical actuators may include at least one component thatresponds to the application of a voltage or current by experiencing achange in volume or position. The change in volume or position mayproduce mechanical work that may act on a fluid source or may betransferred to a fluid source, such that a fluid can be delivered our ofthe fluid source.

In embodiments, the electrochemical actuator may include a positiveelectrode and a negative electrode, at least one of which is anactuating electrode. These and other components of the electrochemicalactuator may form an electrochemical cell, which may initially becharged. The electrochemical cell may begin discharging when a circuitbetween the electrodes is closed, causing the actuating electrode toactuate. The actuating electrode may thereby perform work upon anotherstructure, such as the fluid source or transfer structure associatedwith the fluid source. The work may cause fluid to be pumped orotherwise dispensed from the fluid source into the target.

More specifically, the actuating electrode may experience a change involume or position when the closed circuit is formed, and this change involume of position may perform work upon the fluid source ortransferring structure. For example, the actuating electrode may expand,bend, buckle, fold, cup, elongate, contact, or otherwise experience achange in volume, size, shape, orientation, arrangement, or location,such that at least a portion of the actuating electrode experiences achange in volume or position. In embodiments, the change in volume orposition may be experienced by a portion of the actuating electrode,while the actuating electrode as a whole may experience a contrarychange or no change whatsoever. It is noted that the electrochemicalactuator may actually include a number of electrochemical actuatorsarranged in series, parallel, or some combination thereof. For example,a number of such electrochemical actuators may be stacked together. Asanother example, concurrent or sequenced delivery of multiple agents maybe achieved by including one or more electrochemical actuators acting ontwo or more fluid sources.

FIG. 2 is a schematic of an embodiment of an electrochemical actuator202. As shown, the electrochemical actuator 202 may include a positiveelectrode 210, a negative electrode 212, and an electrolyte 214. Thesecomponents may form an electrochemical cell that is initially dischargedand is then charged before use, or is initially charged, as shown inFIG. 2( a). The position electrode 210 may be configured to expand inthe presence of the electrolyte 214. When a circuit between theelectrodes 210, 212 is closed, current may travel from the positiveelectrode 210 to the negative electrode 212. The positive electrode 210may experience a change in volume, resulting in longitudinaldisplacement of at least a portion of the positive electrode 210, asshown in FIG. 2( b). Thereby, the positive electrode 210 may exert apumping force or pressure on a fluid reservoir 204 or associatedtransfer structure 216, such as the illustrated plate. The pumping forceor pressure may cause fluid to be pumped from the fluid reservoir 204.Thus, the electrochemical actuator 202 may be considered a self-poweredelectrochemical pump. In the illustrated embodiment, the electrochemicalcell has a positive electrode 210 selected to have a lower chemicalpotential for the working ion when the cell is charged, and is therebyable to spontaneously accept working ions from the negative electrode212 as the cell is discharged. In embodiments the working ion includesbut is not limited to the proton or lithium ion. When the working ion islithium, the positive electrode 210 may comprise one or more lithiummetal oxides including LiCoO₂, LiFePO₄, LiNiO₂, LiMn₂O₄, LiMnO₂,LiMnPO₄, Li₄Ti₅O₁₂, and their modified compositions and solid solutions;oxide compound comprising one or more of titanium oxide, manganeseoxide, vanadium oxide, tin oxide, antimony oxide, cobalt oxide, nickeloxide or iron oxide; metal sulfides comprising one or more of TiSi₂,MoSi₂, WSi₂, and their modified compositions and solid solutions; ametal, metal alloy, or intermetallic compound comprising one or more ofaluminium, silver, gold, boron, bismuth, gallium, germanium, indium,lead, antimony, silicon, tin, or zinc; a lithium-metal alloy; or carboncomprising one or more of graphite, a carbon fiber structure, a glassycarbon structure, a highly oriented pyrolytic graphite, or a disorderedcarbon structure. The negative electrode 212 may comprise lithium metal,a lithium metal alloy, or any of the preceding compounds listed aspositive electrode compounds, provided that such compounds when used asa negative electrode are paired with a positive electrode that is ableto spontaneously accept lithium from the negative electrode when thecell is charged. Other configurations are also possible.

In embodiments, the electrochemical actuator may include an anode, acathode, and a species, such as lithium ion. At least one of theelectrodes may be an actuating electrode that includes a first portionand a second portion. The portions may have at least one differingcharacteristic, such that in the presence of a voltage or current, thefirst portion responds to the species in a different manner than thesecond portion. For example, the portions may be formed from differentmaterials, or the portions may differ in thickness, dimension, porosity,density, or surface structure, among others. The electrodes may becharged, and when the circuit is closed, current may travel. The speciesmay, intercalate, de-intercalate, alloy with, oxide, reduce, or platewith the first portion to a different extent than the second portion.Due to the first portion responding differently to the species than thesecond portion, the actuating electrode may experience the change involume or position.

An example of such an embodiment is shown in FIG. 3, which is aschematic view of another embodiment of an electrochemical actuator 302.The electrochemical actuator 3112 may include a positive electrode 310,a negative electrode 312, and a species 314. The species 314 may be anelectrolyte that includes, for example, a lithium ion. The positiveelectrode 310 may include a first portion and a second portion. Thefirst portion may include a material that is dimensionally active whenin the presence of species. For example, aluminum expands upon alloyingwith or being intercalated by lithium. The second portion may include amaterial that is not dimensionally active when in the presence of thespecies, or is relatively less dimensionally active than the material ofthe first portion. For example, copper does not substantiallyintercalate or alloy with lithium. Thus, the positive electrode 310 maybe considered a bimorph structure, with one of the portions serving as apositive current collector.

The negative electrode 312 may serve m a negative current collector. Forexample, the negative electrode 312 may include a layer of lithium metalbonded to or deposited on a layer of copper. Initially, the electrodesmay be charged but may not form a closed circuit, as shown in FIG. 3(a). The positive electrode 310 may have a lower chemical potential forlithium than the negative electrode 312. When the circuit between thetwo electrodes is closed, as shown in FIG. 3( b), current may flowtoward the negative electrode 312. The first portion of the positiveelectrode 310 may alloy or intercalate with the lithium, causing anexpansion in volume, while the second portion may act as a mechanicalconstraint. Thereby, the positive electrode 310 may bend or otherwisedisplace. The displacement of the positive electrode 310 may betransferred to a fluid reservoir 304, causing the fluid reservoir 304 toexpel fluid.

As mentioned above, such an electrochemical actuator may power a fluiddelivery device suited delivering of a drug-containing or non-drugcontaining fluid into a human patient or other target. Such a fluiddelivery system may be embodied in a relatively small, self-contained,and disposable device, such as a patch device that can be removablyattached to the skin of the human body. The patch device may berelatively small and self-contained because the electrochemical actuatorserves as both the battery and a pump. The small and self-containednature of the device advantageously may permit concealing the devicebeneath clothing and may allow the patient to continue normal activityas the drug is delivered. External tubing may not be required tocommunicate fluid from the fluid reservoir into the body, unlikeconventional drug pumps. Instead, any tubing may be contained within thedevice, and a needle or other fluid communicator may extend from thedevice into the body. The electrochemical actuator may initially becharged, and may begin discharging once the patch device is activated topump or otherwise deliver the drug or other fluid into the body. Oncethe electrochemical actuator has completely discharged or the fluidreservoir is empty, the patch device may be removed and discarded. Thesmall and inexpensive nature of the electrochemical actuator and othercomponents of the device may permit disposing of the entire device,unlike conventional pump devices having a pump that is retained. Thus,the device may permit drug delivery, such as subcutaneous or intravenousdrug delivery, over a time period that may vary from several minutes toseveral days. Subsequently, the device maybe removed from the body anddiscarded.

For the purposes of this disclosure, the term “disposable” generallymeans a single use device, or a component thereof, that is intended tobe discarded. Because the electrochemical actuator may serve as abattery, the electrochemical actuator may discharge with use, andthereafter may be discarded. Because the electrochemical actuator alsoserves as the pumping mechanism, however, discarding the electrochemicalactuator also discards the pumping mechanism. Such a configurationdiffers from a conventional infusion pump, which includes a pumpingmechanism that is retained for subsequent reuse. Unlike a conventionalinfusion pump, a patch pump device comprising the electrochemicalactuator may be completely disposable.

Such a device may generally include a drug or fluid delivery systemassociated with a housing. As generally described above, the drugdelivery system may include an electrochemical actuator suited to drivea drug from a fluid reservoir through a needle or other fluidcommunicator. The housing may at least partially contain the fluiddelivery system and may be suit for removably associating the fluiddelivery system with human skin.

So that the device can be worn on the skin, a releasable adhesive may atleast partially coat an underside of the housing. The adhesive may benon-toxic, biocompatible, and releasable from human skin. To protect theadhesive until the device is ready for use, a removable protectivecovering may cover the adhesive, in which case the covering may beremoved before the device is applied to the skin. Alternatively, theadhesive may be heat or pressure sensitive, in which case the adhesivemay be activated once the device is applied to the skin. Exampleadhesives include but are not limited to acrylate based medicaladhesives of the type commonly used to affix medical devices such asbandages to skin. However, the adhesive is not necessary and may beomitted, in which case the housing may be associated with the skin, orgenerally with the body, in any other manner.

The size, shape, and weight of the device may be selected so that thedevice may be comfortably worn on the skin after the device is appliedvia the adhesive. For example, the device may have a size in the rangeof about one inch by about one inch by about 0.1 inches to about fiveinches by about five inches by about one inch, and in some embodimentsin a range of about two inches by about two inches by about 0.25 inchesto about four inches by about four inches by about 0.67 inches. Theweight of the device may be in the range of about five grams to abouttwo hundred grams, and in some embodiments in a range of about fifteengrams to about one hundred grams. The device may be able to dispense avolume in the range of about 0.1 milliliters to about one thousandmilliliters, such as between about 0.5 milliliters and about fivemilliliters. The shape of the device may be selected so that the devicemay be relatively imperceptible under clothing. For example, the housingmay be relatively smooth and free from sharp edges. However, any size,shape, or weight is possible.

The housing may be formed from a material that is relatively lightweightand flexible, yet sturdy. The housing also be may formed from acombination of materials such as to provide specific portions that arerigid and specific portions that are flexible. The material may also berelatively low-cost, so that the device may be disposable. Examplematerials include plastic and rubber materials, such as polystyrene,polybutene, carbonate, urethane rubbers, butene rubbers, silicone, andother comparable materials and mixtures thereof, although a combinationof these materials or any other material may be used.

In embodiments, the housing may include two portions; a base portion anda movable portion. The base portion may be suited for attaching to theskin. For example, the base portion may be relatively flexible. Anadhesive may be deposited on an underside of the base portion, which maybe relatively flat or shaped to mate with a particular body area. Themovable portion may be sized and shaped for association with the baseportion. In embodiments, the two portions may be designed to locktogether, such as via a locking mechanism. In some cases, the twoportions may releasably lock together, such as via a releasable lockingmechanism, so that the movable portion may be removably associated withthe base portion. To assemble the device, the movable portion may bemovable with reference to the base portion between an unassembledposition and an assembled position. In the assembled position, the twoportions may form a device having an outer shape suited for concealingthe device under clothing. Embodiments of such a device are generallydescribed below with reference to FIGS. 4-10, although a range ofconfigurations are possible.

FIG. 4 is a side cross-sectional view of an embodiment of a patch device400. The device 400 generally includes a fluid delivery systemassociated with a housing 418, which may include a base portion 422 anda movable portion 424. An adhesive 420 may be positioned on an undersideof the base portion 422. The movable portion 424 may house one or morecomponents of the fluid delivery system, such as an electrochemicalactuator 402, a fluid reservoir 404, and fluid communicator 406. Themovable portion 424 may be sized and shaped for insertion into the baseportion 422. More specifically, the movable portion 424 may be movablewith the reference to the base portion 422 between an unassembledposition shown in FIG. 4 (a), and an assembled position shown in FIGS.4( b-c). In the assembled position, the two portions 422, 424 may mateand lock together. When assembled, the outer surface of the device 400may be relatively smooth and easy to conceal under clothing.

In the embodiment illustrated in FIG. 4, a releasable locking mechanismis formed by detents 426 located on an exterior surface of the movableportion 424 and a grooved flange 428 located on an interior surface ofthe base portion 422. In the unassembled position, the detents 426 restin the grooved flange 428 to support the movable portion 424 above thebase portion 422. To assemble the device 400, a force F is applied tothe movable portion 424 to push it downward. The force F causes thegrooved flange 428 to flex outward and the detent 426 to travel past thegrooved flange 428. Thus, the movable portion 424 travels further intothe base portion 422 and becomes firmly seated therein. The groovedflange 428 returns to prevent the detent 426 from moving upward,releasable locking the device 400 together. When so assembled, thedevice 400 takes on a bulbous shape that is relatively free from sharpedges. It is noted that, in some embodiments, the locking mechanism maynot be releasable.

In the embodiment shown in FIG. 5, the device 500 generally includes ahousing formed from a base portion 522 and a movable portion 524. Likethe device 400, the base portion 522 may have an adhesive on anunderside for associating the device 500 with the skin (not shown forclarity). A fluid delivery system may generally be contained in themovable portion 524 (not shown for clarity).

More specifically, the base portion 522 may have a relatively ovalexterior and an interior that is sized and shaped to receive the movableportion 524. For example, the movable portion 524 may have a body 530and a projection 532, and the base portion 522 may have an interior slot534 and an opening 536. The interior slot 534 may be sized and shapedfor receiving the projection 532, and the opening 536 may be sized andshaped for receiving the body 530. To assemble the device 500, theprojection 532 may be inserted through the opening 536 along the slot534, as shown in FIG. 5( b). The body 530 may be pressed into theopening 536 so that the movable portion 524 becomes firmly seated in thebase portion 522, as shown in FIG. 5( d). When so assembled, the shapeof the movable portion 524 may naturally limit its upward and rearwardmovement, releasably locking the two portions 522, 524 together. Theassembled device 500 may take on a smooth oval shape that is relativelyfree from the sharp edges and has a relatively low profile, so that thedevice 500 may be concealed under clothing.

In the embodiment shown in FIG. 6, specifically FIG. 6( c) and FIG. 6(d), the device 600 may include a movable portion 624 that snaps onto anexterior of a base portion 622 instead of being inserted therein.Specifically, the base portion 622 may include a base 638 and a guide640 that projects upward from the base 638. The base 638 may be a layerof adhesive, such as a flexible, double-sided layer of adhesive.Alternatively, the base 638 may comprise a plate having an adhesive onan underside. The movable portion 624 may have a cavity that housescomponents of the fluid delivery system, such as an electrochemicalactuator 602, a fluid source 604, and associated electronics 672(embodiments of which are described below with reference to FIG. 10). Arecess 642 may be formed in the movable portion 624 for receiving theguide 640. To assemble the base portion 622 and the movable portion 624,the movable portion 624 may be positioned over the base portion 622 asshown in FIG. 6( c). The guide 640 may locate the recess 642, so thatthe portions 622, 624 are properly aligned. A force may be applied topress the movable portion 624 onto the base portion 622, as shown inFIG. 6( d). The guide 640 and the recess 642 may form a snap fitting,such that the device 600 becomes releasably locked together.Alternatively, the movable portion 624 may adhere to the base portion622, such as in embodiments in which the base 638 is a double-side layerof adhesive. When assembled, the device 600 has a relatively smooth andlow profile exterior that may permit concealing the device beneathclothing.

It should be noted that different embodiments of the device may beassembled using different hand motions. For example, the device 400shown in FIG. 4 may be assembled by exerting a force on the movableportion 424 in a direction generally perpendicular to the surface of theskin, as shown in FIG. 4( b), while the device 500 shown in FIG. 5 maybe assembled by exerting a force on the movable portion 524 in adirection that forms an angle with the surface of the skin, as shown inFIG. 5( b). Thus, different embodiments of the device may be bettersuited for assembly on different parts of the body or with fluidcommunicators inserted at different angles, as further described below.It also should be noted that some embodiments of the device, such as thedevice 400, the device 500, and the device 600 may be assembled usingone hand. Assembling the device with one hand may facilitate attachingthe device to a portion of the body that cannot be accessed easily. Forexample, some drugs or other fluids may be infused through the backsideof the body, which may be difficult to access with both hands.Assembling the device on the backside of the body, for example, may berelatively easy with embodiments of the device that can be assembledusing one hand.

In embodiments, the device may be designed such that assembling thedevice simultaneously inserts the fluid communicator into the body.Specifically, the fluid communicator may initially be retracted insidethe housing and may be transferred from the housing into the body duringassembly of the device. More specifically, the force that causes thehousing to move from the unassembled position to the assembled positionmay also be effective to cause the needle to enter the body.

In the embodiment of the device 400 shown in FIG. 4, for example, thefluid communicator 406 may be a needle extending downward from themovable portion 424. When the device 400 is in the unassembled position,as shown in FIG. 4( a), the needle may be protected inside the baseportion 422. A septum 444 or other penetrable member may be positionedin the base portion 422 adjacent to the needle, enclosing the baseportion 422 so that the needle is not exposed to contaminants. When theforce F is applied to move the movable portion 424 to the assembledposition, as shown in FIG. 4( b), the needle penetrates the septum 444and enters the skin. Because the force F is applied relativelyperpendicular to the surface of the skin, the needle may enter the bodyat an angle that is relatively perpendicular to the surface of the skin.Such a configuration may be suited for patients that prefer insertingthe needle in a perpendicular orientation, or for drugs or other fluidsthat are suited for being delivered via a needle in a perpendicularorientation. However, in other embodiments, other configurations arepossible.

For example, in the embodiments of the device 500 shown in FIG. 5, thefluid communicator 506 may be a needle positioned at the end of theprojection 532. The slot 524 may extend downward through the baseportion 522, forming an angle with an underside of the base portion 522.The slot 534 may terminate in an aperture 546 formed through theunderside of the base portion 522. The projection 532 may be sized suchwhen the projection 532 is positioned in the slot 534, the needle passesthrough the aperture 546 into the skin. To assemble the device 500, theprojection 532 is inserted through the slot 534. The force F is appliedat an angle with reference to the surface of the skin to push theprojection 532 along the slot 534, such that continued application ofthe force F inserts the needle into the body at an angle with referenceto the surface of the skin. Inserting the needle at an angle may bepreferred by some users and/or for some types of drug or fluid delivery.

In the embodiments described above with reference to FIG. 4 and FIG. 5,the force that causes the device to move into the assembled position isthe same force that acts on the needle to insert the needle into thebody. In such embodiments, the needle travels into the body in the samedirection that the movable portion travels into the base portion. Inother embodiments, the device may include mechanics that alter thedirection of the force before the force acts on the needle. In suchembodiments, the force may act on the movable portion in one directionand may act on the needle in another direction. For example, themechanics may alter the direction of a perpendicular force before theforce acts on the needle, so that the force can insert the needle intothe body at an angle. Example mechanics may include a spring and alatch, wherein associating the movable portion with the base portionreleases the latch to cause the spring to insert the needle into thebody. In such embodiments, the mechanics may permit selecting theinsertion angle of the needle, such as by rotating a dial or sliding aslider, so that the user can adjust the insertion angle based on hispersonal preference. A person of skill may be able to design suchmechanics based on the disclosure above.

In still other embodiments, the force that causes the needle to enterthe body may be applied completely separately from the force that placesthe device in the assembled position. For example, the needle may bemanually inserted into the body before the device is associated with theneedle. As another example, the electrochemical actuator may apply aforce to the needle to insert the needle into the body, Further, aseparate insertion mechanism may be provided for inserting the needleinto the body.

Such an embodiment is shown in FIG. 6, specifically with reference toFIG. 6( a) and FIG. 6( b). Specifically, the device 600 may be suitedfor use with a separate needle insertion mechanism 648. The needleinsertion mechanism 648 may be adapted for inserting a fluidcommunicator 606, such as a needle or cannula, through the base portion622 of the device 600 and into the body. For example, the base portion622 may include an opening 650 for receiving the fluid communicator 606,the opening 650 being formed through the guide 640 and the base plate638. To permit aligning the needle insertion mechanism 648 who the baseportion 622, and more specifically, to permit aligning the fluidcommunicator 606 with the opening 650, the needle insertion mechanism648 may include a recess 652 sized and shaped to mate with the guide640.

To insert the fluid communicator 606, the needle insertion mechanism 648may be placed on the base portion 622, as shown in FIG. 6( b). A spring654, which is generally retained within the needle insertion mechanism648 in a compressed state, may be released via a releasable latch 656.The spring 654 may be in communication with the fluid communicator 606may be expel the fluid communicator 606 out of the needle insertionmechanism 648 when the latch 656 is released. The fluid communicator 606may travel through the opening 650, as showing in FIG. 6( b), and intothe body, as shown in FIG. 6( c). Thereafter, the needle insertionmechanism 648 may be removed from the base portion 622, as shown in FIG.6( c), so that the movable portion 624 may be positioned thereon asshowing in FIG. 6( d). The needle insertion mechanism 648 maysubsequently be discarded, or may be saved for re-use depending on theembodiment.

In embodiments, the fluid communicator 606 may be a soft cannula 658. Aneedle 660 may be fixedly associated with the spring 654 to initiallypierce the skin and assist in inserting the soft cannula 658 into thebody, as shown in FIG. 6( b). The needle 660 may subsequently beretracted or removed from the body, leaving the soft cannula 658 intothe body, although the aligning guide 662 is not necessary and may beomitted.

In some embodiments, the needle insertion mechanism may be designed forone handed operation to facilitate inserting the catheter in hard toreach places. Further, the needle insertion mechanism may be designed toinsert the needle at a variety of different angles, including auser-selected angle. Fluid communicators other than needles or softcannulas may be inserted by the needle insertion mechanism, depending onthe embodiment. The needle inserting force may be supplied by the springor in other manners, such as by the user, manually, in which case thespring may be omitted. Although the illustrated needle insertionmechanism is separate from the device, which permits reducing the sizeand/or weight of the device, the needle insertion mechanism may be anintegral part of the device that is retained within the device after theneedle is inserted. It also should be noted that the configurationdescribed above, in which a piercing needle that assists with insertinga soft cannula is subsequently removed from the body, may be employedwith reference to other embodiments.

By way of example, the fluid communicator is described above as being aneedle or a cannula. In embodiments, the needle or a soft cannula may berelatively small for comfort. In other embodiments, the fluidcommunicator can be any catheter or other device for delivering fluidsinto the body, or combinations thereof. In embodiments, the fluidcommunicator may be relatively sterile. Further, the device may be usedin association with a conventional infusion set, in which case the fluidcommunicator may be one or more parts of the infusion set, such as astandard Luer lock or other connector that is adapted to connect thedevice to the infusion set, or the fluid communicator may be omittedcompletely. In another embodiment, the pump patch is not limited tosubcutaneous delivery. For example, the device may be connected to anindwelling infusion port, such as a central venous access port known inthe art, in which case the fluid communicator may be a suitable adaptorfor associating the device with the port. In still another embodiment,the fluid communicator may comprise a microneedle array suitable fortransdermal delivery of fluid drugs, as known in the art.

Although embodiments, of the device are described above as comprisingtwo separate portions that can be assembled together, or two separateportions and a needle insertion mechanism, in other embodiments thedevice may be a single portion or the device may have more than twoseparate portions.

Further, in the embodiments described above, the fluid deliver system isgenerally housed in one portion of the device, namely, the movableportion. In other embodiments, the fluid delivery system may be housedin other portions of the device, such as the base portion, or in acombination of a number of portions of the device, such as a combinationof the base portion and the movable portion. Examples are shown in FIGS.7 and 8. FIG. 7, for example, illustrates an embodiment of a device 700that is generally similar to the device 500. However, the fluid deliverysystem of the device 700 may be split between a base portion 722 and amovable portion 724. In an unassembled position, shown in FIG. 7( a),the base portion 722 may house an electrochemical actuator 702 while themovable portion 724 may house a fluid source 704 and a fluidcommunicator 706. In an assembled position, shown in FIG. 7( b), theelectrochemical actuator 702 may be brought into direct or indirectcommunication with the fluid source 704.

FIG. 8 illustrates an embodiment of a device 800 that is generallysimilar to the device 600. However, the fluid delivery system of thedevice 800 may be split among a base portion 822 and a movable portion824. In an unassembled position, shown in FIG. 8( a), the base portion822 may house an electrochemical actuator 802 and a control system 872.The fluid communicator 806 may also be positioned in the base portion822, after having been inserted via a needle insertion mechanism. Themovable portion 824 may house a fluid source 804. In an assembledposition, shown in FIG. 8( b), the electrochemical actuator 802 may bebrought into direct or indirect communication with the fluid source 804.

Depending on the embodiment, the components of the fluid deliverysystem, including the electrochemical actuator, the fluid source, andthe fluid communicator, may be positioned among various portions of thedevice, such as the base portion, the movable portion, and the needleinsertion mechanism (if present). The components may be separated untilthe device is assembled to achieve selected design criteria, such asincreased safety, decreased cost, or improved quality of life. Forexample, the wet and sterile components, such as the fluid source andfluid communicator, may be separated from the dry and non-sterilecomponents, such as the electrochemical actuator and any associatedelectronics, for safety purposes. Examples of such embodiments includethe device 700 and the device 800.

Some components may be separated to permit reusing one or morecomponents while discarding one or more other components. Suchembodiments may permit disposing of certain spent or damaged portionswhile reusing other fresh and functioning portions. For example, a fluidsource that contains a relatively expensive drug may be separated fromthe electrochemical actuator and/or associated electronics to permitreusing the fluid source if the electrochemical actuator or electronicsare defective. Alternatively, a fluid source that contains a drugdelivered in relatively high volumes may be separated from theelectrochemical actuator and associated electronics to permit reusingthe electrochemical actuator and electronics with multiple fluidsources. As another example, electronics may be separated from the fluidsource and/or electrochemical actuator to permit reusing the electronicseven after the fluid source is empty and/or the electrochemical actuatorhas completely discharged. Further, the fluid communicator may beseparated from one or more other components to permit reusing the othercomponents in the event that needle insertion fails or the needle needsto be changed. An example of such an embodiment is the device 600, whichincludes the associated needle insertion mechanism. Further, somecomponents may be separated to permit un-assembling and reassembling thedevice without reinserting the fluid communicator. Such an embodimentmay permit certain activities, such as shopping and bathing. An exampleof such an embodiment is the device 600. Based on the above disclosure,a range of other configurations are possible. For example, the devicemay include a fluid communicator portion, an electrochemical actuatorportion, a fluid source portion, and an electronics portions. Theseportions may be assembled to form a device of the type described herein,yet may be unassembled and reassembled to substitute and discardportions as necessary.

Alter the device is assembled, the electrochemical actuator may beactivated so that the electrochemical actuator begins discharging, asfurther described below. The electrochemical actuator may actuate as itdischarges, directly or indirectly acting on the fluid source to drivethe fluid into the body. For example, the electrochemical actuator maybe positioned in direct contact with the fluid source, such thatactuation of the electrochemical actuator directly acts on the fluidsource to deliver fluid out of the fluid source. Alternatively, atransferring structure or other appropriate mechanics may be positionedbetween the electrochemical actuator and the fluid source, such thatactuation of the electrochemical actuator is transferred through thetransferring structure to the fluid source. In embodiments, the transferstructure may amplify the change in volume or displacement experiencedby the electrochemical actuator, such that a relatively small change involume or displacement may produce the desired effect upon the fluidsource.

For example, in the embodiment shown in FIG. 4, the electrochemicalactuator 402 may directly act on the fluid source 404. As shown in FIG.4( a), the fluid source 404 may be a deformable bladder or pouchpositioned in direct contact with the electrochemical actuator 402. Whenthe electrochemical actuator 402 actuates, a force or pressure may beapplied to the fluid source 404, causing the fluid source 404 to deform,as shown in FIG. 4( b). The pressure within the fluid source 404 mayincrease, driving the fluid through the fluid communicator 406, as shownin FIG. 4( c).

In the embodiment shown in FIG. 6, the electrochemical actuator 602 mayindirectly act on the fluid source 604 via, for example, a transferstructure 668. As shown in FIG. 6( c), the fluid source 604 may be achamber, and the transfer structure 668 may be a piston in communicationwith the chamber. When the electrochemical actuator 602 actuates, aforce may be applied to the transfer structure 668. In turn, thetransfer structure 668 may apply a force to the fluid source 604 todrive fluid through the fluid communicator 606.

The transfer structure is described as a piston by way of example,although the transfer structure may have any other configurationenvisioned by a person of ordinary skill based on the presentdisclosure. Such a transfer structure may comprise one or more knownmechanical or electrical components arranged in any combination and/orlocation in the device that permits transferring work from theelectrochemical actuator to the fluid source. Including a transferstructure may permit the device to have a range of different shapes,sizes and dimensions, as the electrochemical actuator need not be indirect physical contact with the fluid source.

By way of example, the fluid source is described above as being abladder, reservoir, pouch, chamber or barrel. In other embodiments, thefluid source may be any component capable of retaining a fluid or drugin fluid form. In the illustrated embodiments, the fluid source may notbe refillable, permitting disposal of the device. In other embodiments,the fluid source may be refilled, which may permit reusing at least aportion of the device and/or varying the drug or fluid delivered by thedevice.

In embodiments, the fluid source may be sized to correlate with theelectrochemical potential of the electrochemical actuator. For example,the size and/or volume of the fluid source may be selected so that thefluid source becomes about substantially empty at about the same timethat the electrochemical actuator becomes about substantiallydischarged. Such a configuration may permit reducing the size and/orcost of the device, as the fluid source may not be too large or containtoo much drug in relation to the driving potential of theelectrochemical actuator, and similarly, the electrochemical may not betoo large or contain too much power in relation to the amount of drug inthe fluid source. In other embodiments, the electrochemical actuator maybe oversized with reference to the fluid source. Such a configurationmay be used with relatively expensive drugs to ensure the fluid sourceis about substantially empty before the electrochemical actuatorcompletely discharges, so that waste of the drug is reduced.

Further, the device may include more than one fluid source in someembodiments. Such a configuration may permit using a single device todeliver two or more drugs or fluids. The two or more drugs or fluids maybe delivered discretely, simultaneously, alternating, according to aprogram or schedule, or in any other manner as further described below.In such embodiments, the fluid sources may be associated with the sameor different electrochemical actuators, the same or different fluidcommunicators, the same or different operational electronics, or thesame or different portions of the housing.

One example embodiment is shown in FIG. 17, which is a sidecross-sectional view of an embodiment of a pump device 1700 thatincludes multiple fluid sources 1704 a and 1704 b. The fluid sources1704 a and 1704 b are operated by different electrochemical actuators1702 a and 1702 b, respectively. The device 1700 may be suited fordelivering two or more drugs or fluids in any configuration. Forexample, the device 1700 may be used in embodiments in which a drug isto be delivered at infrequent intervals over an extended period, such asa period of several days. In such an embodiment, one fluid source 1704 amay comprise the drug and the other fluid source 1704 b may comprise afluid such as saline. The saline may be periodically administeredbetween doses of the drug to impede clogs from forming in the fluidcommunicator 1706.

Another example embodiment is shown in FIG. 18, which is a sidecross-sectional view of an embodiment of a pump device 1800 thatincludes multiple fluid sources 1802 a and 1804 b operated by the sameelectrochemical actuator 1802. The device 1800 may be suited fordelivering two or more drugs or fluids in a range of configurations. Forexample, the device 1800 may be used in embodiments in which the drug orfluid has constituent components that are segregated prior to deliveryinto the body. For example, the drug may be stored in a dry powder form(e.g., lyophilized) in one compartment and then shortly or immediatelyprior to administration, it may be reconstituted into a solution orsuspension with a suitable fluid vehicle known in the art, e.g., salinesolution, for delivery. This may be particularly advantageous forcertain drugs, such as biologics or protein drugs, that may preferablybe in a lyophilized or other dry powder form in order to provide drugstability during storage, i.e., shelf stability. In these and in otherembodiments, the fluid source 1802 may comprise a drug storage reservoirsuited to store a drug or other non-fluid that can be reconstituted. Inembodiments, intervening mechanics may transfer and/or amplify thedisplacement of the electrochemical actuator 1802 to each of the fluidsources 1804 a and 1804 b in different manners, permitting differentfluid flow rates from the fluid sources 1804 b and 1804 b. Althoughdevices having two fluid sources are illustrated, one of skill wouldunderstand that more than two fluid sources may be provided in otherembodiments.

Devices having two or more fluid sources may have a number of differentconfigurations within the scope and spirit of the present disclosure.For example, the fluid sources may be separated into different portionsof the housing, which may permit replacing one of the fluid sources at arelatively higher frequency than the other fluid source. Further, theelectrochemical actuator may be substituted with any other pump device,in which case one or more separate batteries may also be provided. Thefluid sources may also have different sizes, shapes, and configurationsdepending on the use of the device.

It should be noted that the electrochemical actuator may be relativelysmall. For example, the electrochemical cell may have a volume in therange of about five cubic millimeters to about ten cubic centimeters,and more specifically in a range of about 0.1 cubic centimeters to aboutone cubic centimeter. The small size of the electrochemical actuator maypermit reducing the size of the device. Further, the electrochemicalactuator may include relatively few parts, reducing the size and cost ofthe device and increasing its reliability. The electrochemical actuatormay power other components of the device. For example, theelectrochemical actuator may power a display, a needle insertionmechanism, or other components of the device. Also, the electrochemicalactuator may be relatively scalable, in a manner analogous toconventional batteries. For example, two or more electrochemicalactuator may be provided, and in embodiments, the electrochemicalactuator may be rechargeable. By way of example, the electrochemicalactuator is described as driving, pumping, or expelling fluid from thefluid source. However, a person of skill would understand that thepresent disclosure encompasses other manners of delivering fluid fromthe fluid source. For example, the electrochemical actuator may pullfluid from the fluid source, such as by creating a vacuum within thefluid source, among other potential configurations. Further, theelectrochemical actuator may be substituted with any known pump or otherdevice suited to cause fluid flow from the fluid source, in which case aseparate power source may also be provided.

The electrochemical actuator may be positioned in an electrical circuitwithin the device. The electrochemical actuator may comprise anelectrochemical cell that is initially charged and actuates as itdischarges. When the electrical circuit is open, the electrochemicalactuator may be prevented from discharging, which may simultaneouslyprevent the electrochemical actuator from actuating. Thereby, fluid maybe prevented from flowing out of the fluid source. When the electricalcircuit is closed, the electrochemical actuator may begin discharging,simultaneously causing the electrochemical actuator to actuate. Thereby,fluid may be permitted to flow out of the fluid source. Thus, fluid maybe expelled from the fluid source when the electrical circuit is closedbut not otherwise.

In embodiments, the electrochemical actuator may discharge and actuateat rates that are dependent upon properties of the electrical circuit.When a property of the electrical circuit is varied, the discharge rateof the electrochemical actuator may be varied, which may simultaneouslyvary the actuation of the electrochemical actuator. Thereby, the fluidflow rate out of the fluid source may be varied. In embodiments, thedevice may include means for controlling or regulating fluid flow fromthe device. The flow control means may be operative to vary propertiesassociated with the electrical circuit, such as to start fluid flow fromthe device, stop fluid flow from the device, and/or vary a rate of fluidflow from the device. Embodiments of flow control means are described indetail below and can be implemented in any combination to permitdelivering drugs according to one or more releases profiles. Releaseprofiles that may be implemented may include release profiles havinglinear flow, non-linear flow, user-initiated flow, feedback responsiveflow, or combinations of these flows, among others. For purposes of thisdisclosure, the term linear flow generally means flow that has arelatively constant flow rate. The term non-linear flow generally meansflow that does not necessarily have a relatively constant flow rate,including modulated flow, pulsatile flow, discontinuous flow, and/orflow that correlates to a program or schedule that may not necessarilyrequire a relatively constant flow rate. The term user-initiated flowgenerally means flow that is initiated in response to an input into thedevice. The term feedback-responsive flow generally means flow thatadjusts in response to one or more sensed conditions, described below.Thus, the pump device may be effective to deliver a wider variety ofdrug therapies than other pump devices.

FIG. 9 is a schematic illustrating an embodiment of an electricalcircuit 900 that may be used to power embodiments of a pump device. Asshown, the electrical circuit 900 may include an electrochemicalactuator 902 positioned in electrical communication with a resistor 980.The electrochemical actuator 902 may comprise an electrochemical cellthat is initially charged at a relatively constant voltage, anddisplaces as it discharges. The resistor 980 may have a relativelyconstant electrical resistance. When the electrical circuit 900 isclosed, as shown, a current 982 may be induced in the electrical circuit900. The electrochemical actuator 902 may begin discharging across theresistor 980, simultaneously causing the electrochemical actuator 902 toactuate. Thereby, fluid may be permitted to flow out of the fluidsource.

More specifically, the discharge of the electrochemical actuator 902 maybe relatively proportional to the current 982 traveling through theelectrical circuit 900, or stated alternatively, the electricalresistance of the resistor 980. Because the electrical resistance of theresistor 980 may be relatively constant, the electrochemical actuator902 may discharge at a relatively constant rate. Thus, the discharge ofthe electrochemical actuator 902 may be relatively linear with thepassage of time, meaning the displacement of the electrochemicalactuator 902 may be relatively linear with the passage of time.

FIG. 10 is a graph illustrating an embodiment of a displacement curve1000, indicating the displacement behavior as a function of time for theelectrochemical actuator 902 positioned in the electrical circuit 900 ofFIG. 9. As shown, the displacement of the electrochemical actuator 902is relatively linear with the passage of time under the conditionsdescribed above. In embodiments, the electrochemical actuator 902 maylinearly displace for a time period that ranges from several minutes toseveral days. For example, the electrochemical actuator 902 may linearlydisplace for a time period in the range of about five minutes to aboutfive weeks, and more specifically in a range of about five hours toabout five days. Thereafter, the linear displacement may taper off andbecome non-linear, as the electrochemical cell reaches a completelydischarged state and the electrochemical actuator 902 stops actuating.

FIG. 11 is a graph illustrating an embodiment of a fluid flow curve1100, indicating the fluid flow behavior as a function of time for afluid source associated with the electrical circuit 900 of FIG. 9.Because the displacement rate of the electrochemical actuator 902 isrelatively constant as shown in FIG. 10, the fluid flow rate from thedevice also may be relatively constant, as shown in FIG. 11. Thus, adevice comprising the electrical circuit 900 may deliver fluid accordingto a relatively continuous release profile, meaning the fluid may flowat a relatively constant rate until the fluid source becomes empty orthe electrochemical actuator becomes completely discharged.

In embodiments, the device may experience a brief priming period atstart-up during which the fluid flow rate mm not be relatively constant.For example, the displacement curve 1000 demonstrates that theelectrochemical actuator 902 may experience a brief priming period whenthe electrochemical actuator 902 is first discharged. During the primingperiod, reaction products may not have accumulated on theelectrochemical actuator 902, preventing the electrochemical actuator902 from displacing linearly. To compensate for such a priming period,the electrochemical actuator 902 may be briefly discharged prior to use,so that when the device is in use, the electrochemical actuator 902 mayexperience relatively linear displacement almost immediately. Further,the fluid flow curve 1100 indicates the fluid source may experience abrief priming period when the electrochemical actuator 902 firstdisplaces. During the priming period, the fluid source may bepressurized and fluid may begin traveling toward the fluid communicator.To compensate for such a priming period, the fluid source may initiallybe pressurized, and a check valve may be provided adjacent to the fluidcommunicator, such that fluid begins flowing through the fluidcommunicator almost immediately after the electrochemical actuatorbegins displacing. For example, the fluid source 604 is not pressurizedin the device 600 shown in FIG. 6( d), and therefore fluid may notinitially flow form the device 600 at a relatively constant rate, butsuch issue may be addressed by pressurizing the fluid source 604 andproviding the check valve adjacent to the fluid communicator 606.

Because the displacement of the electrochemical actuator may berelatively proportional to the current passing through the electricalcircuit, the electrochemical actuator may be relatively easy to control.For example, the displacement of the electrochemical actuator may bevaried by one or more flow control means positioned in the electricalcircuit. Examples of such flow control means include one or moreelectrical contacts, switches, controllers, circuitry components, orcombinations thereof, as further described below. The flow control meansmay be operative to control the electrical circuit. For example, theflow control means may be operative to open or close the electricalcircuit. When the flow control means open the electrical circuit, theelectrochemical actuator may stop discharging and actuating, such thatthe fluid is not expelled from the fluid source. When the flow controlmeans closes the electrical circuit, the electrochemical actuator maybegin discharging and actuating, such that fluid is expelled from thefluid source. The flow control means also may be operative to vary thecurrent through the electrical circuit, such as by varying theresistance of the electrical circuit. When the flow control means variesthe current or the resistance, the electrochemical actuator maydischarge at a varied rate, such that the electrochemical actuatordisplaces at a varied rate to expel from the fluid source at a variedflow rate.

FIG. 12 is a schematic illustrating an embodiment of an electricalcircuit 1200 that includes electrical contacts 1264. The electricalcontacts 1264 may permit the electrochemical actuator 1202 to displacewhen the electrical contacts 1264 are in electrical communication witheach other, but not otherwise. As shown, the electrical contacts 1264are not in electrical communication with each other. Therefore, theelectrical circuit 1200 is broken. The electrochemical actuator 1202 isnot discharging or displacing, and therefore fluid is not flowing. Inembodiments, such electrical contacts 1264 may preserve theelectrochemical actuator 1202 in the charged state until the device isassembled, so that the electrochemical cell may not lose charge untilthe device is to be used. Such electrical contacts 1264 may also preventfluid flow until the device is assembled.

Such an embodiment is shown and described with reference back to FIG. 4.Specifically, the electrical contacts 464 may be positioned in the baseportion 422 and the movable portion 424. The electrical contacts 464 areshown as (+) and (−) for illustrative purposes, although theconfiguration may be reversed in other embodiments. When the device 400is in the unassembled position shown in FIG. 4( a), the electricalcontacts 464 may not contact each other, breaking the electrical circuitto prevent the electrochemical actuator 402 from discharging andactuating. When the device 400 is moved into the assembled positionshown in FIG. 4( b), the electrical contacts 464 may contact each otherto close the electrical circuit, permitting the electrochemical actuator402 to begin discharging and actuating, provided the electrical circuitis not broken in some other place. Subsequently, the electrochemicalactuator 402 may act on the fluid reservoir 404 to deliver fluid out ofthe fluid communicator 406, as shown in FIG. 4( c). It should be notedthat assembling the device 400 may not cause the electrical contacts 464to directly contact each other so that the electrical circuit can beclosed. Alternatively, the electrical contacts may be omittedcompletely, in which case the electrochemical actuator may or may not beprevented from discharging when the device is unassembled.

With reference back to FIG. 12, when the electrical contacts 1264 arepositioned in the electrical circuit 1200 with an electrochemicalactuator 1202 having a relatively constant voltage and a resistor 1280having a relatively constant electrical resistance, fluid may not bedelivered until the device is assembled, and thereafter fluid may bedelivered according to a relatively continuous release profile.Specifically, fluid may begin flowing once the device is assembled andmay continue flowing at a relatively constant rate until theelectrochemical actuator becomes completely discharged or the fluidsource becomes empty. Alternatively, the release profile may be variedby implementing one or more additional flow control means a furtherdescribed below.

FIG. 13 is a schematic illustrating an embodiment of an electricalcircuit 1300 that includes a variable resistor 1380. The variableresistor 1380 may be any electrical component having an electricalresistance that may be altered or controlled. More specifically, varyingthe variable resistor 1380 may vary the current 1382 induced in thecircuit 1300, which in turn may vary the discharge rate of theelectrochemical actuator 1302. Similarly, varying the discharge rate ofthe electrochemical actuator 1302 may vary the displacement rate of theelectrochemical actuator 1302, which in turn may vary the fluid flowrate from the fluid source. Thus, the electrical resistance of thevariable resistor 1380 may be adjusted to control the fluid flow fromthe fluid source. The adjustment in the fluid flow may be proportionalto the adjustment in the electrical resistance, due to the principlesdescribed above.

FIG. 14 is a schematic illustrating an embodiment of an electricalcircuit 1400 that includes a switch 1484. The switch 1484 may beoperative to open or close the electrical circuit 1400. When the switch1484 is closed, the electrochemical actuator 1402 may discharge. Forexample, the electrochemical actuator 1402 may discharge at a relativelyconstant rate in embodiments in which the resistor 1480 has a relativelyconstant electrical resistance. When the switch 1484 is opened, theelectrochemical actuator 1402 may be prevented from discharging, whichprevents the electrochemical actuator 1402 from displacing. Thus, theswitch 1484 may be adjusted to control the fluid flow from the fluidsource.

FIG. 15 is a graph illustrating a displacement curve 1500, indicatingthe displacement behavior as a function of time for a fluid sourceassociated with the electrical circuit 1400 of FIG. 14. The switch 1484may be intermittently opened and closed to vary the duty cycle of theelectrochemical actuator 1402, thereby varying the displacement of theelectrochemical actuator 1402. For example, during a full on cycle, theswitch 1484 may be closed so that the electrochemical actuator 1402 maydisplace at a relatively constant rate. During a duty cycle, the switch1484 may be intermittently opened and closed so that the effectivedisplacement rate of the electrochemical actuator 1402 is relativelylower than the displacement rate during the full on cycle. Specifically,the effective displacement rate may depend upon the amount of time theswitch 1484 spends in the opened and closed positions. The displacementcurve 1500 illustrates the displacement for the electrochemical actuator1402 when the switch 1484 is closed during the duty cycle for 16% of thetime, 33% of the time, and 66% of the time, respectively, although anyconfiguration is possible. As shown, closing the switch 1484 for 66% ofthe time results in a relatively higher effective displacement rate, andtherefore a relatively higher fluid flow rate, than closing the switch1484 for 33% of the time or 16% of the time.

FIG. 16 is a schematic view of an embodiment of a device 1600 thatincludes an embodiment of a control system 1672. The control system 1672may be adapted to control an electrochemical actuator 1602.Specifically, the control system 1672 may vary the displacement of theelectrochemical actuator 1602 to vary the fluid flow rate from a fluidsource 1604, through a fluid communicator 1606, and into a user 1608.For example, the control system 1672 may vary the displacement of theelectrochemical actuator 1602 by opening the circuit, closing thecircuit, or varying the current or resistance of the circuit. Thereby,the control system 1672 may permit administering a selected releaseprofile or altering a release profile. For example, the control system1672 may administer a constant fluid flow rate, a varied fluid flowrate, a continuous fluid flow, a discontinuous fluid flow, a modulatedfluid flow, a pulsed fluid flow, a programmed fluid flow, a scheduledfluid flow, a feedback responsive fluid flow, a user-controlled fluidflow, or a fluid flow that is varied at a rate responsive to abiological or mechanical measure. Therefore, the control system 1672 maypermit safe delivery of the drug therapy in a manner that benefits theuser 1608.

The control system 1672 may comprise one or more flow control means,such as one or more of the electrical contacts, resistor, variableresistor, and switch described above, or other known circuitry componentor combinations thereof. In embodiments, the control system 1672 mayalso comprise a controller and a memory, such as a microcontroller or astate machine. The memory may include a program of operation comprisinga set of instructions executable by the controller. The controller mayexecute the program of operation to vary the current or resistance ofthe electrical circuit according to the set of instructions. Forexample, the controller may be operative to control the one or more flowcontrol means to open the circuit, close the circuit, or vary thecurrent or resistance of the circuit. Thereby, the controller may beoperative to vary the fluid flow from the device to achieve a selectedrelease profile. For example, the release profile may be a programmedrelease profile, a scheduled release profile, or a release profile thatis response to one more inputs received from, for example, a feedbacksystem 1676 or a user interface 168. In embodiments, the control system1672 may be powered by an external power source 1674. The power source1674 may be another electrochemical actuator of suitable voltage,although the power source 1674 may have any other configuration or maybe omitted.

In other embodiments, the flow control means may be arranged within theelectrical circuit to control the circuit in a particular manner as afunction of time, in which case control system 1672 may not include thecontroller and in which case a pre-defined release profile may be“hard-coded” into the electrical circuit.

In embodiments, the control system 1672 may control the electricalcircuit according to the time of day. For example, a schedule may be setby the user. Such an embodiment may permitting controlling due flowaccording to the ciredian rhythm of the body.

In embodiments, the control system 1672 may permit controlling theelectrical circuit in response to inputs received from one or both ofthe feedback system 1676 and the user interface 1678. For example, thecontrol system 1672 may open the circuit, close the circuit, or vary thecurrent or resistance of the circuit in response to the inputs.

The feedback system 1676 may be adapted to measure or otherwise senseone or more conditions associated with the device and/or the user. Forexample, the feedback system 1676 may sense an actual current throughthe electrical circuit, an actual voltage across the electrical circuit,an actual discharge of the electrochemical actuator 1602, an actualdisplacement of the electrochemical actuator 1602, and actual fluid flowout of the fluid source 1604, an actual fluid flow through the fluidcommunicator 1606, an actual current rate through the electricalcircuit, an actual voltage rate across the electrical circuit, an actualdischarge rate of the electrochemical actuator 1602, an actualdisplacement rate of the electrochemical actuator 1602, an actual fluidflow rate out of the fluid flow source 1604, an actual fluid flow ratethrough the fluid communicator 1606, proxies for these conditions, otherconditions, or combinations thereof. For example, the feedback system1676 may comprise one or more sensors known in the art and appropriatelypositioned within the device 1600, such as a strain gauge, a capacitivesensor, a variable resistance sensor, a flow sensor, or a vision sensor,among others. The feedback system 1676 may provide the sensed conditionsto the control system 1676, which may be operative to change thedischarge rate of the electrochemical actuator 1602 in response to thesensed conditions, such as by opening the circuit, closing the circuit,or varying the current or resistance of the circuit. Thereby, thecontrol system 1676 may maintain the desired release profile.

In embodiments, the feedback system 1676 may be in communication withthe user and may sense one or more conditions associated with the user.For example, the feedback system 1676 may remove a bodily fluid from theuser 1608, and in response the control system 1672 may adjust therelease profile. The feedback system 1676 may also be in communicationwith a power source, such as the power source 1674, which may be anotherelectrochemical actuator. In another variation, the feedback system 1676may include a biosensor, e.g., to assess the concentration of one ormore analytes in a physiological fluid of the patient.

As mentioned above, the control system 1672 may be in communication witha user interface 1608. The user interface 1678 may accept one or moreinputs from the user, and the control system 1672 may adjust the releaseprofile in response to the input. The user inputs may comprise one ormore of the following: a request to initiate fluid flow, a request todiscontinue fluid flow, a request to cause temporarily fluid flow, and arequest to vary the fluid flow rate. For example, the device may includeone or more user-responsive controls such as a switch, a button, or aslider. The switch may permit the user to turn the fluid flow on or off,such as by opening or closing the circuit. The button may permit theuser to initiate a temporary fluid flow, such as by temporarily closingthe circuit. The slider may permit the user to vary the flow rate of thefluid flow, such as by varying the current through the electricalcircuit. The user interface 1608 may also include a display, which maydisplay information delivered by the control system 1672, such as thenumber of doses dispensed and/or a number of doses remaining. Suchinformation may be provided to the control system 1672 by, for example,the feedback system 1676.

Thus, the control system 1672 may permit delivering drugs continuously,on-demand, or in a modulated manner. The device may be used, forexample, for continuous delivery of normally injected compounds, for thedelivery of compounds requiring titration and precise control, or foron-demand patient controlled analgesia.

The device 1600 is shown and described by way of example, and otherconfigurations are included within the scope of the present disclosure.For example, the displacement of the electrochemical actuator 1602 maybe transferred to the fluid source 1604 through a transfer mechanism1668 as shown, although the transfer mechanism 1668 may be omitted.Further, the feedback system 1676 and/or the user interlace 1678 may beomitted, in which case the control system 1676 may not be responsive tofeedback or inputs received from the user 1608, respectively.

By way of example, the flow control means are described above ascontrolling the fluid flow from the device by controlling the dischargeof the electrochemical actuator. Such embodiments may preserve thepotential of the electrochemical actuator, such that discharge of theelectrochemical actuator results in correlated fluid flow. In otherembodiments, the electrochemical actuator may actuate as it charges, inwhich case charging the electrochemical actuator results in correlatedfluid flow. In still other embodiments, the flow control means maycontrol the fluid flow by controlling the transfer structure or otherintervening mechanics between the electrochemical actuator and the fluidsource. In such embodiments, the electrochemical actuator maycontinuously discharge, but transfer of the correlated displacement maybe interrupted or reduced in amplification by the transfer mechanism. Aperson of skill may be able to implement such a configuration based onthe above disclosure.

Upon reading the present disclosure, a person of skill would appreciatedthat the described embodiments of the device are merely illustrativeexamples that convey the scope and breadth of the present disclosure.Other embodiments of the device that combine portions of the embodimentsdescribed above are included within the scope of the present disclosure.

Embodiments of the present device may be used to deliver a variety ofdrugs according to one or more release profiles. For example, the drugmay be delivered according to a relatively uniform flow rate, a variedflow rate, a preprogrammed flow rate, a modulated flow rate, in responseto conditions sensed by the device, in response to a request or otherinput from a user or other external source, or combinations thereof.Thus, embodiments of the present device may be used to deliver drugshaving a short half-life, drugs having a narrow therapeutic window,drugs delivered via on-demand dosing, normally-injected compounds forwhich other delivery modes such as continuous delivery are desired,drugs requiring titration and precise control, and drugs whosetherapeutic effectiveness is improved through modulation delivery ordelivery at a non-uniform flow rate. These drugs may already haveappropriate existing injectable formulations.

For example, the present devices may be useful in a wide variety oftherapies. Representative examples include, but are not limited to,insulin delivery tor Type 1 or Type 2 diabetes; leutenizing hormonereleasing hormone (LHRH) or follicle stimulating hormone (FSH) forinfertility: immunoglobulin for autoimmune diseases; apomorphine forParkinson's disease; interferon A for chronic hepatitis B, chronichepatitis C, solid or hematologic malignancies; antibodies tor thetreatment of cancer; octreotide for acromegaly; ketamine for pain,refractory depression, or neuropathic pain; heparin for post-surgicalblood thinning; corticosteroid (e.g., prednisone, hydrocortisone,dexamethasone) for treatment of MS; morphine, hydromorphone, fentanyl orother opioids or non-opioids for post-operative pain or for chronic andbreakthrough pain; and tizanidine for spasticity (e.g., MS, SCI, etc.).

In a particular embodiment, the device may be used to administerketamine for the treatment of refractory depression or other mooddisorders. In embodiments, ketamine may include either the racernate,single enantiomer (R/S), or the metabolite (wherein S-norketamine may beactive).

In another particular embodiment, an embodiment of the device herein maybe used for administration of Interferon A tor the treatment ofhepatitis C. In one embodiment, a several hour infusion patch is wornduring the day or overnight three times per week, or a continuousdelivery system is worn 24 hours per day. Such a device mayadvantageously may replace bolus injection with a slow infusion,reducing side effects and allowing the patient to tolerate higher doses.In other Interferon A therapies, the device may also be used in thetreatment of malignant melanoma, renal cell carcinoma, hairy cellleukemia, chronic hepatitis B, condylomata acuminata, follicular(non-Hodgkin's lymphoma, and AIDS-related Kaposi's sarcoma.

In still another particular embodiment, an embodiment of the devicedescribed herein may be used for administration of apomorphine or otherdopamine agonists in the treatment of Parkinson's Disease (“PD”).Currently, a bolus subcutaneous injection of apomorphine may be used toquickly jolt a PD patient out of an “off” state. However, apomorphinehas a relatively short half-life and relatively severe side effects,limiting its use. The device described herein may provide continuousdelivery and may dramatically reduce side effects associated with bothapomorphine and dopamine fluctuation. In one particular embodiment, thedevice provides continuous delivery of apomorphine or other dopamineagonist, with, optionally, an adjustable baseline and/or a bolus buttonfor treating an “off” state in the patient. Advantageously, this methodof treatment may provide improved dopaminergic levels in the body, suchas fewer dyskinetic events, fewer “off” states, less total time in “off”states, less cycling between “on” and “off” states, and reduced need forlevodopa; quick recovery from “off” state if it occurs; and reduced oreliminated nausea/vomiting side effect of apomorphine, resulting fromslow steady infusion rather than bolus dosing.

In yet another embodiment, an embodiment of the device may be used foradministration of an analgesic, such as morphine, hydromorphone,fentanyl or other opioids, in the treatment of pain. Advantageously, thedevice may provide improved comfort in a less cumbersome and/or lessinvasive technique, such as for post-operative pain management.Particularly, the device may be configured for patient-controlledanalgesia.

Publications cited herein and the materials for which they are cited arespecifically incorporated by reference. Modifications and variations ofthe methods and devices described herein will be obvious to thoseskilled in the art from the foregoing detailed description. Suchmodifications and variations are intended to come within the scope ofthe appended claims.

1. A patch pump device comprising: at least one fluid source; a fluidcommunicator in fluid communication with the at least one fluid source;and an electrochemical actuator operative to cause fluid to be deliveredfrom the at least one fluid source into the fluid communicator. 2-53.(canceled)